CD24通过调节肝内Ly6C^(lo)巨噬细胞亚群中PDGF-B的分泌抑制肝纤维化进程  

CD24 inhibits the liver fibrosis process by regulating the secretion of PDGF-B in hepatic Ly6C^(lo) macrophage subset

作　　者：靳悦 汪河 李明威 张学军 JIN Yue;WANG He;LI Ming-wei;ZHANG Xue-jun(Department of Immunology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学基础医学院免疫学系,天津300070

出　　处：《天津医科大学学报》2022年第3期260-265,共6页Journal of Tianjin Medical University

基　　金：国家自然科学基金面上项目(31370891);天津市自然科学基金重点项目(18JCZDJC98300)。

摘　　要：目的:探讨CD24分子在胆总管结扎(BDL)诱导的小鼠胆汁淤积型肝纤维化中对肝内Ly6C^(lo)巨噬细胞亚群的调节以及分泌PDGF-B的影响。方法:建立小鼠胆总管结扎诱导的肝纤维化模型,将野生型(WT)与CD24基因敲除(CD24^(-/-))雌性小鼠随机分为造模组(BDL)与假手术组(Sham),每组5只,造模组进行胆总管结扎,假手术组与造模组手术处理相同但不结扎胆总管。术后7 d应用HE和天狼星红(Sirius Red)染色分析小鼠肝组织病理变化和肝纤维化程度,定量-PCR(Q-PCR)和Western印迹检测肝内α-SMA等纤维化因子的表达,流式细胞术分析CD24分子在肝内巨噬细胞亚群中的表达,共培养实验检测肝内星状细胞中纤维化因子的变化。结果:两种基因背景小鼠的假手术组无病理表现,在造模组中,CD24^(-/-)小鼠与WT小鼠相比肝纤维化明显加重,表现为肝汇管区炎性细胞浸润增多,α-SMA等肝纤维化标志物的表达升高。流式分析结果显示,CD24分子在肝内Ly6C^(lo)巨噬细胞亚群上高表达,在造模组中,CD24^(-/-)鼠造模后肝内Ly6C^(lo)巨噬细胞亚群比例[(65.05±0.250)%]高于WT鼠[(52.55±2.950)]%,差异有统计学意义(P<0.05)。进一步研究发现:PDGF-B在肝内Ly6C^(lo)巨噬细胞亚群高表达,并且在CD24^(-/-)小鼠中的表达明显高于WT小鼠,差异有统计学意义(P<0.0001)。结论:CD24分子可通过调节肝内Ly6C^(lo)巨噬细胞亚群中PDGF-B分泌减缓肝纤维化进程。Objective:To investigate the effect of CD24 on Ly6C^(lo)macrophage subsets and secretion of PDGF-B in cholestatic liver fibrosis induced by common bile duct ligation(BDL).Methods:A mouse model of BDL-induced liver fibrosis was established.Wild type(WT)and CD24 gene knockout(CD24^(-/-))female mice were randomly divided into model(BDL)group and sham group,with 5 mice in each group.The model group was subjected to common bile duct ligation.The sham group was the samesurgical treatment as that of model group,but the common bile duct was not ligated.Seven days after operation,the pathological changes of liver tissue and the degree of liver fibrosis were analyzed by HE and Sirius red staining.The expression of fibrosis factors such asα-SMA were detected by Western blotting and Q-PCR.The expression of CD24 in hepatic macrophages subsets was detected by flow cytometry.Co-culture assay was used to detect the changes of fibrotic factors in hepatic stellate cells.Results:There were no pathological manifestations in the sham operation group of mice with two genetic backgrounds.In the model group,the hepatic fibrosis of CD24^(-/-)mice was significantly worse than that of WT mice,CD24^(-/-)mice had more inflammatory cell infiltration in hepatic portal area,elevatedα-SMA and other markers of hepatic fibrosis expression.Flow cytometry analysis showed that CD24 was highly expressed in Ly6C^(lo) macrophage subsets in liver.The proportion of Ly6C^(lo) macrophage subsets of CD24^(-/-)mice[(65.05±0.250)%]was higher than WT mice[(52.55±2.950)%],and the difference was statistically significant(P<0.05).Further study found that PDGF-B was highly expressed in Ly6C^(lo) macrophage subsets in liver,and the expression in CD24^(-/-)mice was significantly higher than WT mice(P<0.0001).Conclusion:CD24 may alleviate the process of liver fibrosis by regulating the secretion of PDGF-B in hepatic Ly6C^(lo) macrophage subset.

关 键 词：CD24分子 肝纤维化 肝内Ly6C^(lo)巨噬细胞 肝星状细胞 PDGF-B 

分 类 号：R392.1[医药卫生—免疫学]